Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
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鉴定通过关键途径介导雄激素信号传导的新型 AR 靶向 MicroRNA，以调节前列腺癌中的细胞活力
DOI：
10.1371/journal.pone.0056592
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Mo W;Zhang J;Li X;Meng D;Gao Y;Yang S;Wan X;Zhou C;Guo F;Huang Y;Amente S;Avvedimento EV;Xie Y;Li Y
MicroRNAs（miRNAs）被认为与前列腺癌（PCa）的发生有密切关系。由于雄激素受体（AR）在前列腺癌的发生和发展中起着重要作用，因此有必要系统地阐明AR和miRNA之间的因果关系，重点是miRNA介导AR信号传导的分子机制。在这项研究中，我们进行了一系列的时程微阵列，以观察在雄激素刺激的前列腺癌LNCaP细胞中mRNA和miRNA的动态全基因组表达平行。因此，我们引入了反应评分来鉴定AR靶miRNA，以及调节评分来鉴定miRNA靶mRNA。基于理论鉴定和实验验证，阐明了3种新识别为AR靶点的miRNA在PCa中解决细胞活力的新机制。(1)miR-19 a被AR直接上调，并分别抑制SUZ 12、RAB 13、SC 4 MOL、PSAP和ABCA 1。(2)miR-27 a被AR直接上调，并抑制ABCA 1和PDS 5 B。(3)miR-133 b被AR直接上调，并分别抑制CDC 2L 5、PTAL 3、RB 1CC 1和CPNE 3。此外，我们发现miR-133 b对PCa细胞存活至关重要。我们的研究通过影响关键途径，特别是通过突破雄激素对正常前列腺组织的生长限制作用，为miRNAs介导的AR信号转导细胞活力提供了某些线索。
MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen’s growth restriction effect on normal prostate tissue.
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影响因子：
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作者：
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